The specific goals of this research are to isolate and characterize the chemical structure and biochemical role of the human histocompatibility antigens, those substances involved in the phenomenon of rejection of transplanted tissue. The research objectives are summarized as follows: 1) to purify several HLA antigens (HLA-A, -B, -C, and -D locus products) from the surface of cultured human lymphocyte cell lines, using both detergent and papain solubilization; 2) to carry out structural studies on purified HLA antigens in order to examine the question of the nature of the specific immunological determinant in each; 3) to sequence the heavy chain of several HLA antigens in order to determine the extent of sequence homology to human immunoglobulins; 4) to study the cleavage of the detergent-solubilized HLA antigens by papain and to study the nature of the fragments released by papain to determine how these molecules are inserted into the lymphocyte membrane; 5) to study the nature of homology among the products of the major histocompatibility complex in man (i.e., HLA-A, -B, -C, and -D loci antigens); 6) to study aspects of pathology relating to HLA antigens, /otably the linkage between HLA-B27 and susceptibility to several autoimmune diseases, and the high linkage between the Singapore-2 allele and susceptibility to nasopharyngeal carcinoma; and 7) to study functions of HLA antigens, possibly in cell-cell interactions in the immune response and in differentiation.